rs1285830362

Variant names:

• chr7-107045103-G-A
• rs1285830362
• NM_002736.3:c.196G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-107045103-G-A
• chr7-107045103-G-C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_002736.3(PRKAR2B):​c.196G>A​(p.Gly66Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000582 in 1,374,288 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000058 (0 hom.)
• Consequence: PRKAR2B NM_002736.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.09
• Publications: 1 publications found

Genes affected

PRKAR2B (HGNC:9392): (protein kinase cAMP-dependent type II regulatory subunit beta) cAMP is a signaling molecule important for a variety of cellular functions. cAMP exerts its effects by activating the cAMP-dependent protein kinase, which transduces the signal through phosphorylation of different target proteins. The inactive kinase holoenzyme is a tetramer composed of two regulatory and two catalytic subunits. cAMP causes the dissociation of the inactive holoenzyme into a dimer of regulatory subunits bound to four cAMP and two free monomeric catalytic subunits. Four different regulatory subunits and three catalytic subunits have been identified in humans. The protein encoded by this gene is one of the regulatory subunits. This subunit can be phosphorylated by the activated catalytic subunit. This subunit has been shown to interact with and suppress the transcriptional activity of the cAMP responsive element binding protein 1 (CREB1) in activated T cells. Knockout studies in mice suggest that this subunit may play an important role in regulating energy balance and adiposity. The studies also suggest that this subunit may mediate the gene induction and cataleptic behavior induced by haloperidol. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.27306566).
• BS2: High AC in GnomAdExome4 at 8 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002736.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKAR2B	NM_002736.3	MANE Select	c.196G>A	p.Gly66Arg	missense	Exon 1 of 11	NP_002727.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKAR2B	ENST00000265717.5	TSL:1 MANE Select	c.196G>A	p.Gly66Arg	missense	Exon 1 of 11	ENSP00000265717.4	P31323
	PRKAR2B	ENST00000854598.1		c.196G>A	p.Gly66Arg	missense	Exon 1 of 12	ENSP00000524657.1
	PRKAR2B	ENST00000913925.1		c.196G>A	p.Gly66Arg	missense	Exon 1 of 11	ENSP00000583984.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000778 AC: 1 AN: 128456 AF XY: 0.0000142

Gnomad AFR exome AF: 0.000171

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000582 AC: 8 AN: 1374288 Hom.: 0 Cov.: 34 AF XY: 0.00000444 AC XY: 3 AN XY: 676386

African (AFR) AF: 0.0000644 AC: 2 AN: 31056

American (AMR) AF: 0.00 AC: 0 AN: 35314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24960

East Asian (EAS) AF: 0.00 AC: 0 AN: 35366

South Asian (SAS) AF: 0.00 AC: 0 AN: 78680

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35920

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4442

European-Non Finnish (NFE) AF: 0.00000560 AC: 6 AN: 1071386

Other (OTH) AF: 0.00 AC: 0 AN: 57164

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.066
FATHMM_MKL	Uncertain	0.90	D
M_CAP	Pathogenic	0.63	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.1
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.28	N
REVEL	Uncertain	0.35
Sift	Benign	0.41	T
Sift4G	Benign	0.63	T
Polyphen		0.39	B
Vest4		0.16
MutPred		0.30		Gain of MoRF binding (P = 0.0073)
MVP		0.77
MPC		1.1
ClinPred		0.37	T
GERP RS		4.1
PromoterAI		-0.023	Neutral
Varity_R		0.16
gMVP		0.41
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1285830362; hg19: chr7-106685548;